Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome
van der Kroef, Maarten; van den Hoogen, Lucas L.; Mertens, Jorre S.; Blokland, Sofie L.M.; Haskett, Scott; Devaprasad, Abhinandan; Carvalheiro, Tiago; Chouri, Eleni; Vazirpanah, Nadia; Cossu, Marta; Wichers, Catherina G.K.; Silva-Cardoso, Sandra C.; Affandi, Alsya J.; Bekker, Cornelis P.J.; Lopes, Ana P.; Hillen, Maarten R.; Bonte-Mineur, Femke; Kok, Marc R.; Beretta, Lorenzo; Rossato, Marzia; Mingueneau, Michaël; van Roon, Joel A.G.; Radstake, Timothy R.D.J.
(2020) European Journal of Immunology, volume 50, issue 1, pp. 119 - 129
(Article)
Abstract
Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 patients with these SADs and 44 healty controls (HC) using mass-cytometry and assessed the diagnostic value of these
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results. Alterations in the frequency of immune-cell subsets were present in all SADs compared to HC. Most alterations, including a decrease of CD56hi NK-cells in SSc and IgM+ Bcells in pSS, were disease specific; only a reduced frequency of plasmacytoid dendritic cells was common between all SADs Strikingly, hierarchical clustering of SSc patients identified 4 clusters associated with different clinical phenotypes, and 9 of the 12 cell subset-alterations in SSc were also present during the preclinical-phase of the disease. Additionally, we found a strong association between the use of prednisone and alterations in B-cell subsets. Although differences in immune-cell frequencies between these SADs are apparent, the discriminative value thereof is too low for diagnostic purposes. Within each disease, mass cytometry analyses revealed distinct patterns between endophenotypes. Given the lack of tools enabling early diagnosis of SSc, our results justify further research into the value of cellular phenotyping as a diagnostic aid.
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Keywords: CyTOF, immunophenotyping, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, Lupus Erythematosus, Systemic/diagnosis, Humans, Middle Aged, Flow Cytometry/methods, Male, Phenotype, Scleroderma, Systemic/diagnosis, Adult, Female, Aged, Sjogren's Syndrome/diagnosis, Sjogren's syndrome, Immunology and Allergy, Immunology, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 0014-2980
Publisher: Wiley-VCH Verlag
Note: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
(Peer reviewed)